Affiliation:
1. Departamento de Biologı́a Funcional e Instituto Universitario de Biotecnologı́a de Asturias (I.U.B.A.-C.S.I.C.), Universidad de Oviedo, 33006 Oviedo, Spain
Abstract
ABSTRACT
Sequencing of a 4.3-kb DNA region from the chromosome of
Streptomyces argillaceus
, a mithramycin producer, revealed the presence of two open reading frames (ORFs). The first one (
orfA
) codes for a protein that resembles several transport proteins. The second one (
mtmR
) codes for a protein similar to positive regulators involved in antibiotic biosynthesis (DnrI, SnoA, ActII-orf4, CcaR, and RedD) belonging to the
Streptomyces
antibiotic regulatory protein (SARP) family. Both ORFs are separated by a 1.9-kb, apparently noncoding region. Replacement of the
mtmR
region by an antibiotic resistance cassette completely abolished mithramycin biosynthesis. Expression of
mtmR
in a high-copy-number vector in
S. argillaceus
caused a 16-fold increase in mithramycin production. The
mtmR
gene restored actinorhodin production in
Streptomyces coelicolor
JF1 mutant, in which the actinorhodin-specific activator ActII-orf4 is inactive, and also stimulated actinorhodin production by
Streptomyces lividans
TK21. A 241-bp region located 1.9 kb upstream of
mtmR
was found to be repeated approximately 50 kb downstream of
mtmR
at the other end of the mithramycin gene cluster. A model to explain a possible route for the acquisition of the mithramycin gene cluster by
S. argillaceus
is proposed.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
62 articles.
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